To examine the relative roles of gene mutation and other possible forms of clonal inheritance in somatic cells, we are studying the origin of drug-resistant variants in haploid cell cultures (cell line ICR 2A, haploid grass-frog (Rana pipiens) embryos). We are examining the mode of origin and biochemical properties of haploid and diploid variants resistant to pyrimidine analogs, to ouabain or to microtubule-depolymerizing alkaloids. The work is to include the separation and study, using affinity chromatography, of multiple forms of thymidine kinase and deoxycytidine kinase expressed in haploid cells and their bromodeoxyuridine and cytosine arabinoside-resistant derivatives. As part of this work, we are using C-band and G-band methods for frog chromosomes developed in the last year of this work to prepare detailed maps of the cytological markers in ICR 2A and to compare these to similar maps of chromosomes from primary cell cultures and from karyotypically altered haploid ICR 2A derivatives. BIBLIOGRAPHIC REFERENCES: J.J. Freed and B.M. Ohlsson-Wilhelm. Cultured haploid cells resistant to antitubulins. In: Microtubules and Microtubule Inhibitors. M. Borgers and M. DeBrabander, eds., North-Holland, Amsterdam. pp. 367-378 (1975). J.J. Freed and I.M. Hames. Loss of a thermolabile thymidine kinase activity in bromodeoxyuridine resistant (transport deficient, kinase positive) haploid cultured frog cells. Exp. Cell Res. 99:126-134 (1976).